Hepion Pharmaceuticals (NASDAQ:HEPA) dosed the first stage 3 (F3) NASH subject with rencofilstat in a Phase 2 clinical trial designed to measure hepatic function.
The trial is being conducted in collaboration with HepQuant and Summit Clinical Research at up to 20 sites in Summit’s integrated research organization.
ALTITUDE-NASH is a Phase 2, randomized, multi-center, open-label study to evaluate the safety and efficacy of rencofilstat in 60 adult subjects. Subjects included in the trial will be presumed F3, based on either historical biopsy or by using the AGILE 3+ criteria as defined by a screening Fibroscan score alongside common clinical and laboratory parameters.
Subjects will be randomized to receive a once daily, oral dose of 75 mg, 150 mg, or 225 mg rencofilstat soft gelatin capsules, with 20 subjects in each dosing cohort, over a period of four months.
The HepQuant SHUNT test, a measure of hepatic function, will be performed at baseline, and changes in disease severity index (DSI), relative to baseline measurements, will be determined at days 60 and 120. Other NASH biomarkers will be collected throughout the study duration.
“When evaluating hepatic drug efficacy, clinicians and regulatory agencies rely on the assessment of many parameters, including liver fat content, inflammation, ballooning, and fibrosis, which require an invasive liver biopsy,” Greg Everson, M.D., CEO and CMO of HepQuant, said in a statement.
Dr. Everson said that while biopsy is the gold standard, it measures only surrogates to liver function and does not truly determine the extent of hepatic impairment or improvement with clinical interventions.
He explained that HepQuant’s non-invasive, blood-based technology determines a DSI score that relies on liver-specific uptake of cholate to measure hepatic and portal blood flow; and portal-systemic shunt in patients with chronic liver disease, providing a direct assessment of liver function and physiology.
To date, HepQuant’s procedure has been successfully utilized in 26 studies with over 1,100 subjects.
Stephen Harrison, M.D., president of Summit, said NASH is the most rapidly increasing indication for liver transplantation in the U.S., and is a leading cause of end-stage liver disease and liver transplantation in adults under the age of 50.
Up to one-third of adults around the world have non-alcoholic fatty liver disease and data within the United States suggest that up to 14% of adults have NASH, a serious liver disease that may progress to cirrhosis and is currently without an FDA approved therapy, he added.
“Given this major unmet medical need, I welcome any advance in the treatment of this serious condition,” Dr. Harrison said. “As a hepatologist and gastroenterologist, I also look forward to the development and adoption of non-invasive testing methods that are able to assess liver function accurately and reliably.”
Todd Hobbs, M.D, CMO of Hepion, said that following the positive Phase 2a AMBITION trial data readouts, Hepion’s clinical team has spent the “better part of the last year preparing for the start of what we expect to be two very informative clinical trials in NASH F3 subjects.”
The ALTITUDE-NASH trial will offer a very sensitive measure of hepatic function at all three doses of rencofilstat. “When combined with data from the recently announced Phase 2b ‘ASCEND-NASH’ paired-biopsy trial in F3 subjects, data from ALTITUDE-NASH will provide us with a better understanding of how rencofilstat impacts several key NASH biomarkers,” Dr. Hobbs said.